title: Galsulfase (Naglazyme®) therapy in infants with mucopolysaccharidosis VI.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of two dose levels of galsulfase (Naglazyme®) in infants with MPS VI.
  
  
  METHODS
  This was a phase 4, multicenter, multinational, open-label, two-dose level study. Subjects were randomized 1:1 to receive weekly infusions of 1.0 or 2.0 mg/kg of galsulfase for a minimum of 52 weeks. Progression of skeletal dysplasia was determined by monitoring physical appearance, radiographic changes, and growth. Urinary glycosaminoglycan (GAG) levels, gross and fine motor function, cardiac function, vision, hearing, and health resource utilization were evaluated. Safety assessments were performed.
  
  
  RESULTS
  Four infants (aged 3.3-12.7 months) participated in the study. Galsulfase was well tolerated at 1.0 and 2.0 mg/kg/week dose levels with no drug-related serious adverse events. Two subjects experienced a total of four possible treatment-related adverse events which were all considered mild. Length and weight remained within age-expected norms. Skeletal abnormalities continued to progress in all subjects. High baseline urinary GAG levels (mean: 870 μg/mg creatinine) decreased by approximately 70%; these reduced levels were maintained (mean: 220 μg/mg creatinine at week 52) despite the development of anti-galsulfase antibodies. Hearing, cardiac function, hepatosplenomegaly, and facial dysmorphism stabilized or improved, but corneal clouding progressed. There was no clear difference in safety or efficacy between the two doses.
  
  
  CONCLUSIONS
  Galsulfase at two dose levels was safe and well tolerated in infants. Normal growth was maintained but skeletal abnormalities continued to progress. Urinary GAG levels decreased with treatment. Early initiation of galsulfase may prevent or slow progression of some disease manifestations.
authors.affiliation: Children's Hospital & Research Center Oakland, 747 52nd Street, Oakland, CA, USA, pharmatz@mail.cho.org.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Harmatz
authors.forename: Paula
authors.initials: P
authors.lastname: Garcia
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guffon
authors.forename: Linda M
authors.initials: LM
authors.lastname: Randolph
authors.forename: Renée
authors.initials: R
authors.lastname: Shediac
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Braunlin
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Lachman
authors.forename: Celeste
authors.initials: C
authors.lastname: Decker
mesh_terms: D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D056947:Enzyme Replacement Therapy / Q000379:methods*; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D009087:Mucopolysaccharidosis VI / Q000188:drug therapy*; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011994:Recombinant Proteins; D020051:N-Acetylgalactosamine-4-Sulfatase; C508864:galsulfase